Abstract
Low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 monoclonal antibody alirocumab may be affected by background statin dose due to increased PCSK9 levels with higher statin doses. Data from 8 Phase 3 trials conducted with background statin (n = 4629) were pooled by alirocumab dose (75 or 150 mg every 2 weeks) and control (placebo/ezetimibe), and analyzed by background statin type/dose. Overall, 58.4% received high-dose statins (atorvastatin 40–80 mg, rosuvastatin 20–40 mg, simvastatin 80 mg), 28.6% moderate-dose statins (atorvastatin 20–<40 mg, rosuvastatin 10–<20 mg, simvastatin 40–<80 mg), and 12.9% low-dose statins (atorvastatin <20 mg, rosuvastatin <10 mg, simvastatin <40 mg). Mean baseline PCSK9 levels were higher with high versus moderate and low statin doses (318.5 vs 280.6 ng/mL). Baseline LDL-C levels were similar across pools, regardless of statin intensity. No associations were observed between statin type/dose and LDL-C % change from baseline or % of patients achieving LDL-C goals at Week 24 for alirocumab versus control (interaction P-values non-significant). Incidence of adverse events was similar for alirocumab versus control, except for a higher rate of injection-site reactions with alirocumab. In summary, alirocumab provided consistent LDL-C reductions and was generally well tolerated independent of background statin type/dose.
Highlights
Statins (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors) are currently the first-line therapy for reducing levels of low-density lipoprotein cholesterol (LDL-C) and reducing cardiovascular risk[1,2,3]
We investigated whether Low-density lipoprotein cholesterol (LDL-C) reductions following alirocumab treatment were affected by background statin dose and type of statin, using pooled data from the ODYSSEY clinical trials programme which was mainly conducted on a background of maximally tolerated statin
The current analysis tested the hypothesis that the LDL-C-lowering efficacy of a given dose of alirocumab may be reduced when administered with a higher versus lower dose of statin therapy, due to increased proprotein convertase subtilisin/kexin type 9 (PCSK9) levels at higher statin doses
Summary
Statins (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors) are currently the first-line therapy for reducing levels of low-density lipoprotein cholesterol (LDL-C) and reducing cardiovascular risk[1,2,3]. Inhibition of PCSK9 with the monoclonal antibody alirocumab reduces LDL-C levels by ~50–60% when added to a statin (with or without other lipid-lowering therapy [LLT]) in Phase 3 clinical trials[10,11,12,13,14,15]. Alirocumab was approved in the USA and Europe in 2015 for treating high-risk patients who require additional reduction in LDL-C beyond that achieved with maximally tolerated statin and other LLTs16,17. The efficacy of monoclonal antibodies to PCSK9 could potentially be impacted by higher versus lower statin doses due to increased PCSK9 levels and target-mediated clearance[19]. We investigated whether LDL-C reductions following alirocumab treatment were affected by background statin dose and type of statin, using pooled data from the ODYSSEY clinical trials programme which was mainly conducted on a background of maximally tolerated statin
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call